A Case of a Relapsing Remitting Macrophage Activating Syndrome After Covid-19 Vaccine In a Teenager with UNC13D Heterozygous Variant of Uncertain Significance

Introduction: Macrophage activation syndrome (MAS) is a severe hyper inflammatory condition caused by the over-activation and proliferation of T cells, NK cells and macrophages. It is often associated with complications of rheumatic/immune diseases. We present a case of a 15-year-old female who experiences recurrent episodes of MAS without any known definitive underlying etiology. Case Presentation: A 15-year-old previously healthy female developed fatigue, fevers, myalgia, chest pain, splenomegaly and lymphadenopathy 10 days after receiving her first Pfizer COVID-19 vaccine. Her symptoms recurred 10 days after receiving the second dose. Her myocarditis, MIS-C, and infectious work up was negative except for positive EBV IgG. Laboratory studies revealed anemia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. She initially responded to decadron;however, her symptoms recurred with steroid taper. Bone marrow biopsy revealed hemophagocytosis. Whole exome sequencing (WES) revealed a heterozygous variant of uncertain significance in UNC13D c.962C>A (p.Thr321Asn). She had multiple re-admissions with significantly elevated inflammatory markers, including extremely high IL2-R, IL-18 and CXCL9. Each episode was complicated by an acute viral infection. She responds to high dose steroids, anti-IL-1, and JAK inhibitors. Nonetheless, it has been difficult to wean decadron without triggering a flare. She continues to require increasing doses of baricitinib. Discussion(s): MAS may be seen as a complication of rheumatic diseases, as well as inborn errors of immunity. However, none of these conditions have been diagnosed in this patient despite extensive testing, including WES. The degree of her immune dysregulation has been very severe making her disease process unpredictable and extremely difficult to control. She has frequent flares precipitated by viral infections or attempts at adjusting her immunomodulators. Weaning her medications has been challenging as she continues to require increasing doses of baricitinib and corticosteroids. The UNC13D gene is associated with autosomal recessive familial hemophagocytic lymphohistiocytosis type 3 (FHL3). Our patient is heterozygous for an UNC13D variant of uncertain significance. Additional genetic inquiries with whole genome sequencing to help elucidate the underlying etiology of her severe condition is being conducted. We hypothesize she developed MAS due to a combination of genetic predisposition, prior EBV infection, and immune stress associated with the COVID-19 vaccine. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023 Elsevier Inc.

Hypofibrinogenemia in a Patient with Cardiogenic Shock, Left Ventricular (Lv) Thrombus, Covid-19, and Severe Liver Injury: A Case Report of Complex Decision Making in the Setting of Multiorgan Failure with Unclear Causality

Background We present a case of a young male with new severe cardiomyopathy requiring critical care within 24 hours. Case A Latino male with alcoholism was admitted for COVID and severe liver injury due to alcohol-induced hepatitis. Within hours, he developed hypoxia, worsening metabolic acidosis with undetectable bicarbonate level and partial respiratory compensation, coagulopathy, acute kidney injury, right lower lobe infiltrates without pulmonary embolism. Reduced ejection fraction heart failure at 15-20% with a large left ventricle apical thrombus was also found. Worsening signs of cariogenic shock despite sustaining normal blood pressure was identified on a physical exam. The patient was transferred to ICU with confirmation of cardiogenic shock with right ventricular failure with Swan-Ganz Catheter. With Concern for impending fulminant liver failure, transfer to a tertiary care center for emergent liver transplant was initiated. Decision-making The dichotomy of requirement for anti-coagulation for LV thrombus with cardiogenic shock and worsening coagulopathy due to liver failure was a challenge. Decision was made to transfuse blood products as needed with goal fibrinogen of 150 mg/dl, later changed to 100-120 mg/dl with heparin. Liver enzymes were down-trending, but it was difficult to determine if this was due to recovery or worsening of liver failure with stabilization of hemodynamics. While awaiting transfer, he developed acute cerebrovascular accident requiring emergent mechanical thrombectomy of a left MCA occlusion with suspension of heparin complicated by acute large intraventricular and intraparenchymal hemorrhage with rapid decline in neurological function. The family declined decompressive craniotomy with evacuation of parenchymal hemorrhage and the patient was transitioned to comfort care measures. Conclusion There are no clear guidelines for transfusion of plasma-based blood products in the setting of cardiogenic shock and liver disease. Expert opinion recommends maintaining fibrinogen levels above 100-200 mg/dl, however, this is in the setting of acute blood loss and is not studied in patients with liver disease. Further studies are needed.Copyright © 2023 American College of Cardiology Foundation

Predictive factors for severe placental damage in pregnant women with SARS-CoV-2 infection.

INTRODUCTION: SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions. METHODS: We retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings. RESULTS: Twelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant. DISCUSSION: In these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes.

Dynamics of hemostasis system's parameters in patients with severe course of Covid-19 undergoing extracorporeal membrane oxygenation

Background: Extracorporeal membrane oxygenation's (ECMO) support causes various hemostatic disorders that are poorly understood, especially in COVID-19 patients with severe acute respiratory distress syndrome (ARDS) Aims: To assess changes in hemostasis parameters during and without ECMO support in COVID-19 patients with severe ARDS Methods: A prospective study of 122 patients with a severe course of COVID-19 was carried out. The average age was 59 +/- 12 years. The patients' condition, assessed by the NEWS and SOFA severity score, was 4.5 +/- 1.4 and 6.1 +/- 1.3 points, respectively. Retro-prospective study of 130 patients with a severe course of COVID-19 requiring the use of ECMO was carried out. The average age of patients was 55 +/- 6 years. The patients' condition, assessed by the RESP and SOFA severity score, was 1 +/- 2 and 10 +/- 2 points respectively. Median ECMO duration was 8 [IQR 4-14] days and median time from intubation to ECMO start was 1 [IQR 1-3] day. All patients were examined for PT, FG, Pr C, AT III, D-dimer and platelet count. The research was performed on day 1 and 7 after ECMO application. Statistical analysis was carried out using Statistica 10.0 software. Result(s): On day 1 patients with ECMO showed a significant decrease in the level of FG, PT, platelet count and the activity of AT III (p < 0.05) and an increase in the level of D-dimer (p < 0.05). On day 7 there was also a decrease in the level of FG and PT, the activity of AT III, Pr C and an increase in the level of D-dimer. Conclusion(s): ECMO triggers early activation of coagulation, which leads to the consumption of FG, PT and platelets, followed by hypofibrinogenemia and thrombocytopenia that may possibly contribute to the high rate of hemorrhagic complications. On the other hand, a decrease in the activity of AT III and Pr C may contribute to thrombotic complications.

AN UNUSUAL CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS ASSOCIATED WITH M.CHIMAERA OR LARGE CELL NEUROENDOCRINE CARCINOMA

CASE: 56-year-old Caucasian male presented to the hospital with worsening weakness, exertional dyspnea, dry and nonproductive cough, and a 5-pound weight loss in 2 weeks associated with loss of appetite. He has a significant medical history of mitral valve repair in July 2014, status post bioprosthetic mitral valve replacement in August 2019- culture-negative treated with ceftriaxone, vancomycin, and doxycycline for 6 weeks complicated with CVA, atrial flutter, tobacco abuse, alcohol abuse. His shortness of breath worsened quickly with O2 saturations dropping to 85% and had to be placed on BiPAP followed by high flow nasal cannula/ noninvasive ventilation and became febrile. He was then transferred to ICU for acute hypoxemic respiratory failure. Differentials could be very broad ranging from infections like visceral leishmaniasis, atypical/tuberculous mycobacteria, histoplasmosis, Ehrlichia, Bartonella, Brucella, adeno, disseminated HSV, hematological like Langerhans cell histiocytosis, multicentric Castleman disease. In this patient, differentials included hemophagocytic lymphohistiocytosis, COVID-19. Covid was negative x2. His lab abnormalities as well as diagnostic testing revealed hemophagocytic lymphohistiocytosis. He was empirically started on antibiotics and dexamethasone 20 mg to be continued for 2 weeks then taper if the patient has continued improvement. Dexamethasone was tapered over 8 weeks. On later admissions, Carious test was positive for M. chimaera, and core biopsy of the lung nodule showed large cell neuroendocrine carcinoma. IMPACT/DISCUSSION: Hemophagocytic lymphohistiocytosis (HLH) is a rare but very dangerous condition, characterized by abnormal activation of the immune system, causing hemophagocytosis, inflammation, and potentially widespread organ damage. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity, is most commonly seen in children. Secondary HLH is commonly associated with infections or malignancies. Most current information on diagnosis and treatment is based on pediatric populations. The HLH-2004 diagnostic criteria are the most commonly used diagnostic criteria and were developed for children;but used in adults as commonly as in children, although there is a gap in the knowledge. The HLH-2004 diagnosis criteria state that diagnosis of HLH can be established if either a molecular diagnosis is made consistent with HLH or diagnostic criteria for HLH is fulfilled, which includes meeting 5 of 8 criteria. These are lab and clinical findings including fever, splenomegaly, significant cytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in bone marrow/spleen or lymph nodes, low or no NK cell activity, ferritin >500 ug/L or sCD25 >2400 U/mL. CONCLUSION: HLH is a disease that needs to be diagnosed and treated promptly, it is fatal otherwise. Treatment is mostly tailored to the patient's root cause, treat the cause, and symptomatic treatment with dexamethasone and etoposide.

Hemorrhagic complications of а novel coronavirus infection: actual clinical problem

Hypercoagulable character of coagulopathy associated with the novel coronavirus infection COVID-19, and the high risk of associated thrombotic complications is a well-known fact. However, there are also case reports of hemorrhagic events in COVID patients in the literature. The review summarizes the publications describing bleedings in coronavirus infection;their overall frequency is on average 4–8%. Gastrointestinal bleeding are prevalent, intermuscular hematomas and hemorrhages in the skin and mucous membranes are frequent. The predictive role of anticoagulants use in therapeutic doses and hypofibrinogenemia is shown. The absence of clear understanding of the pathophysiological mechanisms is noted. © Simarova I. B., Perehodov S. N., Bulanov A.Yu., 2021 © Gemostaz i Reologia LLC, 2021.